1.1- Diols ketals

Following a published procedure [1], perchloric acid was used as catalyst in preparing a diol ketal, and was neutralised with sodium hydrogencarbonate before workup. Some sodium perchlorate remained dissolved after filtering the reaction mixture, and dining subsequent vacuum distillation (with the bath temperature increasing to 200°C) an explosion occurred. 

Bromo-7-hydroxycoumar-4-yl]-l,3-dioxalane (Bhc-diol) Ketal, 470 4-Trimethylsilyl-l,3-dioxolane, 470 0,0 -Phenylenedioxy Ketal, 470... 

The l-ch]oropropane-2,3-diol ketal of cyclohexanone was subjected to Gabriel amination to give (78) which was converted to the valuable antihypertensive guanadrel (79) by the Rathke reaction Scheme 5.19.) [85], This is a peripherally active adrenergic neurone blocker comparable to guanethidine or methyldopa, but is claimed to avoid their side-effects [86, 87]. It is effective and well-tolerated for treatment of h rtension in the elderly [88]. 

Epimino-16 3,23- epoxy-23a-ethoxy- 5a,25otff-cholest- 22(AO-en-3p,20a-diol ketal) Fig. 7.20 (deriv.) S. lycopersicum L. x S. hirsutum Dun. [syn. L esculentum Mill. X L. hirsutum (Dun.) Macbride] (3)... 

I60C-Hydroxy Derivatives of Gorticoids and their Acetonides. The preparation of 16a-hydroxy-9a-fluoroprednisolone (48) from the 3,20-bisethylene ketal of hydrocortisone acetate (49) has been reported (73). The latter was dehydrated with thionyl chloride in pyridine to yield the 4,9(11),16-triene (50). The 16,17-unsaturated linkage was selectively hydroxylated with OsO /pyridine to yield the 16a,17a-diol (51), which was converted... 

Acetals andKetals. Acetals of 1,3-diols are prepared by refluxing the diol with the aldehyde in the presence of an acid catalyst, even in an aqueous medium. The corresponding ketals are more difficult to prepare in aqueous solution, but cycHc ketals of neopentyl glycol, eg, 2-butyl-2-ethyl-5,5-dimethyl-l,3-dioxane (3), can be prepared if the water of reaction is removed azeotropicaHy (34). 

CH2=C(OBn)(CH3), POCI3 or TsOH, 61-98% yield. It should be noted that these conditions do not afford a cyclic acetal with a 1,3-diol. This ketal is stable to LiAlH4, diisobutylaluminum hydride, NaOH, alkyllithiums, and Grignard reagents. 

Acetonide formation is the most commonly used protection for 1,2- and 1,3-diols. The acetonide has been used extensively in carbohydrate chemistiy to mask selectively the hydroxyls of the many different sugars. In preparing acetonides of triols, the 1,2-derivative is generally favored over the 1,3-derivative, but the extent to which the 1,2-acetonide is favored is dependent on stmcture. Note that the 1,2-selectivity for the ketal from 3-pentanone is better than that from acetone. ... 

Cyclic g-haloacetals and -ketals have been prepared by variations on two basic methods. The most frequently used method involves the combination of an a,B-unsaturated carbonyl compound (acrolein, methyl vinyl ketone, croton-aldehyde, etc.) a diol, and the anhydrous hydrogen halide. All possible sequences of combining these three have been used. In most cases the... 

Selective hydroxylation with osmium tetroxide (one equivalent in ether-pyridine at 0 ) converts (27) to a solid mixture of stereoisomeric diols (28a) which can be converted to the corresponding secondary monotoluene-sulfonate (28b) by treatment with /7-toluenesulfonyl chloride in methylene dichloride-pyridine and then by pinacol rearrangement in tetrahydrofuran-lithium perchlorate -calcium carbonate into the unconjugated cyclohepte-none (29) in 41-48 % over-all yield from (27). Mild acid-catalyzed hydrolysis of the ketal-ketone (29) removes the ketal more drastic conditions by heating at 100° in 2 hydrochloric acid for 24 hr gives the conjugated diketone (30). 

Cyano-17-hydroxyandrost-4-en-3-one, 135 20-Cy ano-21 -hydroxy-5/3-pregn-17(20) -ene-3,11-dione 21-raethyl ether, 224 10 -Cyano-19-norandrost-5-ene-3,17-dione bis-ethylene ketal, 278 10 -Cyano-19-norpregn-5-ene- 3/3,20/3-diol diacetate, 270... 

Butylethylidene and 1-phenylethylidene ketals were prepared selectively from the C4-C6, 1,3-diol in glucose by an acid-catalyzed transketalization reaction [e.g., Me3CC(OMe)2CH3, TsOH/DMF, 24 h, 79% yield PhC(OMe)2Me, TsOH, DMF, 24 h, 90% yield, respectively]. They are cleaved by acidic hydrolysis AcOH, 20°, 90 min, 100% yield, and AcOH, 20°, 3 days, 100% yield, respectively. Ozonolysis of the /-butylmethylidene ketal affords hydroxy ester, albeit with poor regiocontrol, but a more sterically differentiated derivative may give better selectivity, as was observed with the ethylidene ketal. ... 

Compounds i, ii, and iii can be prepared by an acid-catalyzed reaction of a diol and the cycloalkanone in the presence of ethyl orthoformate and mesitylene-sulfonic acid. The relative ease of acid-catalyzed hydrolysis [0.53 M H2SO4, H2O, PrOH (65 35), 20°] for compounds i, iii, acetonide, and ii is C5 C7 > acetonide C (e.g., t.//s for 1,2-O-alkylidene-a-D-glucopyranoses of C5, C7, acetonide, and C derivatives are 8, 10, 20, and 124 h, respectively). The efficiency of cleavage seems to be dependent upon the electronic environment about the ketal. ... 

As with the benzylidene ketals, the carbonate can be opened to give a monoprotected diol. ... 

H2Sil2, CDCI3, —42°, 1-10 min, 100% yield. Aromatic ketals are cleaved faster than the corresponding aliphatic derivatives, and cyclic ketals are cleaved more slowly than the acyclic analogues, such as dimethyl ketals. Substituted ketals such as those derived from butane-2,3-diol, which react only slowly with Mc3SiI, can also be cleaved with H2Sil2. If the reaction is run at 22°, ketals and acetals are reduced to iodides in excellent yield. 

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